Treatment of the elderly with epilepsy

By | January 11, 2015

Older adults have increased steadily in number and proportion of the total world population. In the United States, the population aged 65 and older numbered 35 million in 2000 and is expected to more than double by 2050. The older population was 12% of the total population in 2000 and will increase to 20% by 2050. The increase in the size of America’s older population is accompanied by rapid growth in the ‘oldest old’ or the population aged 85 and older. The oldest old comprised 12.1% of the older adult population in 2001, up from 9.9% in 1991. The population aged 85 and older is currently the fastest-growing segment of the older population and is expected to grow faster than any other age group. The United States Census Bureau projections suggest that the oldest old population could grow from about 4 million in 2000 to 19 million by 2050. By 2050, nearly 24% of the older population is projected to be age 85 and older. The size of this segment of the population is especially important for the future of healthcare systems because those individuals older than 85 years tend to be in poorer health and require more services than the ‘younger’ old individuals.

The issue of older adults is most apparent when it pertains to neurological illnesses. Older patients tend to suffer from a disproportionate number of neurological conditions, including seizures and epilepsy. It is important to understand that there are several aspects of seizures in older adults that tend to be more or less confined to this age group and require special consideration in order to deliver the best care and ensure quality of life.

Older patients with seizures can be differentiated from younger ones based on five separate variables that are unique to older adults. These are: (i) epidemiology; (ii) aetiology; (iii) seizure presentation; (iv) pharmacokinetic and pharmacodynamic differences; and (v) psychosocial concerns. This chapter will explore these areas and discuss in detail diagnosis, management, therapy and the psychosocial concerns relating to the older adult with epilepsy.

Therapy

Therapy is initiated when the risk of recurrence is high and the risk of injury from a seizure outweighs the risk of anti-epileptic drug toxicity. Older patients tend to have a higher risk of seizure recurrence after a single seizure. In one study by Luhdorf and colleagues, 75% of 151 older patients studied proceeded to have a second seizure. Therefore, as patients grow older, the risk of subsequent seizures rises, and is greater than that of younger patients. Often, medications can be initiated after one seizure if the presenting seizure was SE, there is an underlying cause such as a cortical infarction with haemorrhage, cortical tumour, or the presence of focal or generalized epileptiform discharges on EEC After a decision is made to initiate medication, it will be important to choose the most appropriate anti-epileptic drug. The reader is referred to other chapters in this book for a more detailed review of anti-epileptic drugs. The following discussion on anti-epileptic drugs will pertain only to those issues that are unique to the older adult.

Simple partial, complex partial, secondary generalized tonic-clonic and myoclonic are the most common seizure types in the aged. Therefore, agents that are approved for use for those seizure types are the best choices as initial therapy. First-line therapy for simple partial and complex partial seizures includes carbamazepine, gabapentin, levetiracetam, lamotrigine, phenobarbital, pregabalin, phenytoin, tiagabine, topiramate, valproic acid and zonisamide. Primary agents approved for generalized tonic-clonic events include phenytoin, topiramate, levetiracetam, lamotrigine, valproic acid and zonisamide. Primary agents available for myoclonic seizures include benzodiazepines, felbamate, levetiracetam, topiramate, valproic acid and zonisamide. The choice of any of these agents is appropriate. Adverse effects and drug interactions are more important than efficacy variables in deciding which agent to utilize.

Anti-epileptic drugs in older adults

As previously discussed, older adults have more co-morbidities and multiple pathologies than the younger adult. Because of this, patients are often taking other medications, and the treatment of seizures can lead to complex polypharmacy. Moreover, older adults are more susceptible to cognitive adverse effects. It appears that the elderly therefore have a narrowed therapeutic window, and are not able to tolerate the higher end of what would be considered the therapeutic range in younger patients (e.g. phenytoin levels over 15 or carbamazepine levels over 10). Thus, one has to be cautious with dosing of an anti-epileptic drug in individuals older than 65, and in general, lower doses should be used initially. Compliance with the drug regimen coupled with serum anti-epileptic drug levels that are not representative of this age group should all be considered when managing anti-epileptic drug therapy.

Best evidence for choosing anti-epileptic drugs in the older adult

Therapeutic monitoring with serum anti-epileptic drug levels

Measuring anti-epileptic drug concentrations is important in epilepsy management for two reasons: (i) assessment of compliance and (ii) ascertaining toxicity. Monitoring anti-epileptic drug levels becomes even more important in the aged because older patients may have memory problems or fail to comply with the drug regimen. Pharmacokinetic changes associated with advanced age include variable absorption, reduced renal and hepatic clearance and reduced serum albumin, which may contribute to more variability in the relationship between dose and serum concentration. Over- or under-dosing may be prevented by checking serum anti-epileptic drug concentrations. However, there are problems in utilizing published serum level ranges for anti-epileptic drugs. Anti-epileptic drug levels represent younger patient data and therefore may not be applicable to older adults. There is evidence that older adults may be more sensitive to the sedative and cognitive effects of benzodiazepines than younger patients with similar drug concentrations. The narrowed therapeutic window may place them at a greater risk for toxicity if one strictly adheres to anti-epileptic drug levels. Therefore, when checking serum concentrations, one must remember that these are likely to be useful in identifying non-compliance and pharmacokinetic issues, but should not be over-interpreted when defining an optimal therapeutic level. It follows that levels that appear to be low may actually be appropriate for the older adult. Clinical presentation rather than laboratory values should be guiding anti-epileptic drug dose decisions.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) has been approved in the treatment of epilepsy (). In this procedure, the carotid sheath is opened and two spiral electrodes are wrapped around the vagus nerve and connected to an infraclavicular generator pack. In experienced surgical hands, the procedure has a duration of less than 1 hour. The implanted device is a programmable stimulator, with the stimulation programmed in advance so that patients may turn the device on or off at any time by placing a magnet against the implant site. The mechanism of the anti-epileptic effect of the vagus nerve stimulator is not known. The efficacy of the procedure compares favourably with medication. The average seizure reduction is 31% at 3 months with 50-60% of patients achieving at least a 50% reduction by 1 year. Adverse effects are few, consisting of hoarseness, coughing and paraesthesias. There may be an impact on sleep. Three studies have addressed VNS in older adults. All have found that there are no unique adverse effects associated with older adults with epilepsy.

Recently, the vagus nerve stimulator has been approved for use for refractory depression. Considering that depression is a common condition found in older adults, this maybe a useful device in the older adult population in patients who have both epilepsy and depression. More studies are needed to address whether VNS has increased efficacy over drugs in older adults. VNS is a reasonable choice in individuals who have failed to respond to medications, and there are no increased surgical complications associated with its use in the older adult group.

Resective Surgery For Epilepsy In Older Adults

In 15-20% of all epilepsy patients, seizures are not completely controlled by medical therapy. Some of these patients can be candidates for surgical treatment. In younger adults, temporal lobectomy, the most common surgical procedure for epilepsy, is readily performed in most settings and its efficacy and safety have been well documented. However, the percentage of older adults that are refractory to all medications is unknown. The VA Cooperative Studies found that the proportion of older adults with intractable epilepsy is small. This study addressed epilepsy of younger onset, which is pathophysiologically distinct from older-onset epilepsy. Because older adults are different, one cannot assume that their response to resective surgery is the same as younger adults.

Four studies have investigated resective epilepsy surgery in older vs. younger adults. Sirven and colleagues evaluated a total of 340 patients aged 50 years and younger and compared them with 30 patients older than 50 years, all of whom had anterior temporal lobectomy for refractory epilepsy. Seizure outcome, neuropsychological test scores and change in driving status were analysed. Age and duration of epilepsy related independently to outcome, but laterality of interictal sharp waves, an early epilepsy risk factor, and presence of tumour were not. Sixteen patients (52%) in the older group and 257 patients (75.6%) in the younger group (P< 0.008) were seizure free. Post-operative neuropsychological outcome and driving status were similar in both the older and younger patients. The study concluded that older patients can indeed have successful epilepsy surgery; however, there is an increased risk of neuropsychological adverse effects.

Grivas and colleagues evaluated 52 patients older than 50 years who underwent temporal lobectomy between 1991 and 2002. The mean age of operation was 55 years with the mean duration of epilepsy at 33 years. They found that 37 older patients attained complete seizure control (71%) and only 10 patients had rare post-operative seizures (19%). The same rate of seizure control was attained by the patients older than age 60 at the time of surgery. These results were not significantly different from those in the younger patient cohort. A trend toward better seizure control was noted in 16 patients with an epilepsy duration of less than 30 years and in 20 patients with a seizure frequency of fewer than five per month. Four per cent of older patients had permanent neurological morbidity, primarily hemiparesis and dysphasia. Hemianopsia occurred in 6% of patients. Neuropsychological testing revealed low pre-operative performances and some gradual deterioration after surgery. The authors concluded that the results of surgery for temporal lobectomy are promising in patients older than 60 years of age, despite a long seizure history.

Similarly to the Sirven study, they found that the risk of complications is somewhat higher compared with that in a younger control group. The finding of lower post-operative neuropsychological performance is a cause for concern. The debate will probably continue as to whether epilepsy surgery should be performed in older adults. Clearly, more care must be taken with epilepsy surgery evaluations before any decision is made to proceed with a resective procedure. Nevertheless, some individuals can benefit from surgery.

When to discontinue treatment

One of the more common consultation questions that neurologists face is when an anti-epileptic drug can be stopped in older adults. Unfortunately, there are no clear answers to this question. There have been studies that have evaluated discontinuation of anti-epileptic drugs in younger patients, but these have not specifically addressed the older adult population. No definitive guidelines or evidence exists to clearly define when to discontinue seizure medications in older adults. Some general suggestions can be made to help the clinician. It is best to confirm the diagnosis of seizures. Often, medications are initiated for conditions which may appear to be epilepsy and may have been incorrectly diagnosed. Confirming the diagnosis of epilepsy ensures that the agent is being utilized appropriately. A patient should be seizure free for a minimum of 2-5 years to maximize the chance of success. It is important to have normal imaging. The EEG should lack epileptiform sharp waves. There must be no history of status epilepticus. More studies are needed to address this important clinical scenario.

Selections from the book: “Therapeutic Strategies in Epilepsy” (2008)